Reproductive failure is a serious problem that has been addressed clinically by in vitro fertilization (IVF) and embryo transfer (ET). These procedures might be expected to yield exceptionally high conception rates as in vitro fertilization provides an already fertilized ova for transfer into a fully primed recipient. Despite these efforts the success rate of IVF/ET is less than ideal. In the published data for IVF/ET in the United States and Canada in 1994, there were 26,961 initiated cycles of standard IVF. Of these, 86.2% led to a retrieval and of these 90.2% led to a transfer. However, the overall success rate in terms of clinical pregnancies was 22.7% per initiated cycle and a 29.1% pregnancy rate per transfer. Additionally, there appears to be a high incidence of early pregnancy loss after in vitro fertilization with a biochemical pregnancy rate of 18% and a spontaneous abortion rate of 27%. Thus, it appears that the IVF technique has been well optimized but implantation failure may be the cause for a large number of losses with ET and this implantational loss is an area of potential improvement.
The factors which contribute to the success of in vitro fertilization/embryo transfer (IVF/ET) have been extensively studied. In looking at what factors may affect implantation, many studies have reported correlations of hormonal or measurement of other parameters with conception rate. High conception rates have been associated with lowered follicular phase PP14 concentrations, large increases in PP14 concentrations from the day of hCG stimulation to the day of embryo transfer, high preretrieval concentrations of CA-125, large increases in CA-125 from the day of hCG stimulation to oocyte retrieval, increased uterine blood flow, increased uterine artery impedance, and an inhibition of uterine motility in the periimplantation period. It has also been suggested that lowered estradiol concentrations at the time of ovulation induction lowered progesterone concentrations at the time of hCG stimulation, or the magnitude of the increase in progesterone in response to hCG stimulation have a higher success of conception. These reports generally fail to determine the mechanism by which these observations are translated into impaired conception.
Few studies have examined the relationship between granulosa lutein cell culture and the characteristics of the cycle from which cells were obtained. One group found that decreased granulosa cell 11 beta hydroxysteroid dehydrogenase activity was associated with higher conception rates. It was reasoned that exposure of the oocyte to cortisol was necessary for proper functional maturation and high amounts of enzyme in the cumulus cells could prevent this exposure. Another study was based upon observations that the magnitude of rise in progesterone concentrations in response to hCG stimulation was correlated with implantation success. They found that patients with an increase of 3 fold in response to hCG were more likely to get pregnant (46%) than those with a P4 increase of less than 3 fold who had only a 14% conception rate. Granulosa lutein cell culture from these patients showed differences in hormone production. Patients with a large serum P4 increase had higher progesterone concentrations in culture. Patients with a low P4 increase had more variable estrogen concentrations in culture but the estrogen was more responsive to gonadotropin stimulation.